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Biomedical subjects

M Myers

Publications and source records attributed to M Myers.

At least 19 recordsLinked to original sources

Characterization of the V0 domain of the coated vesicle (H+)-ATPase.

The coated vesicle (H+)-ATPase is composed of two domains, a peripheral V1 domain containing the 73 (A subunit)-, 58 (B subunit)-, 40-, 34-, and 33-kDa subunits and an integral V0 domain containing the 100-, 38-, 19-, and 17 (c subunit)-kDa subunits (Adachi, I., Puopolo, K., Marquez-Sterling, N., Arai, H., and Forgac, M. (1990) J. Biol. Chem. 265, 967-973). In the present manuscript we characterize the V0 domain with respect to its structural and activity properties. Glycerol density gradient separation of solubilized coated vesicle membrane proteins reveals the presence of an excess of V0 domains which migrate with a molecular weight of 250,000 and contain the V0 polypeptides in the same stoichiometry as in the intact V1V0 complex. Like the c subunit in V1V0, the c subunit of the free V0 domain is labeled by [14C]N,N'-dicyclohexylcarbodiimide (DCCD) and is extracted by chloroform:methanol. In addition, a monoclonal antibody specific for the 100-kDa subunit of the intact (H+)-ATPase recognizes the 100-kDa subunit of V0. Tryptic cleavage of the V0 complex gives the same pattern of fragments for the 100- and 38-kDa subunits as in the intact complex, but with an increase in sensitivity, suggesting greater exposure of these subunits in free V0. Proton conduction was measured in reconstituted vesicles containing the V0 domain and in native vesicles stripped of V1. No DCCD-inhibitable proton conduction was observed in either preparation, suggesting that unlike the corresponding F0 domain of F1F0, the free V0 domain is not an open proton channel.

Animals

Strontium-90 as an indicator of time since death: a pilot investigation.

The results of a pilot investigation are presented. The study aimed to show that the presence of radioactive strontium-90 in human bone could be used as evidence of active uptake during life. In this way the time since death of the individual could be identified as occurring before or after the date when atmospheric levels of radioactive strontium were at a peak in the early 1960s. The results of this initial investigation were encouraging but further detailed analysis is required on a substantially larger sample of material spanning a more controlled time period.

Bone and Bones

High dose oral amiodarone loading: electrophysiologic effects and clinical tolerance.

Although amiodarone is an effective drug for the treatment of life-threatening ventricular arrhythmias, no standard oral loading dose protocol has been defined, and patients often undergo prolonged hospitalization for amiodarone loading. High dose (greater than 1,800 mg/day) oral loading has usually been reserved for unstable patients with incessant ventricular tachyarrhythmias. The current study was designed to 1) examine the clinical and electrophysiologic effects of a high dose oral amiodarone loading regimen in more stable patients; and 2) ascertain its safety and tolerance, possibly allowing shortened amiodarone loading periods and potentially decreased length of hospital stay. The study group included 16 patients with a history of recurrent ventricular arrhythmias and decreased left ventricular function, who were refractory to prior antiarrhythmic drug therapy. The oral loading protocol was 50 mg/kg per day of amiodarone for 3 days, then 30 mg/kg per day for 2 days, followed by maintenance therapy of 300 to 400 mg twice daily. Electrophysiologic testing was performed at baseline, on days 1 and 5 and during week 6. Amiodarone and desethylamiodarone levels were measured and symptoms monitored. Clinically, the high dose loading protocol was well tolerated in 15 of the 16 patients. Arrhythmias were rendered noninducible by day 1 in three patients and remained noninducible throughout the study period in two of the three. The remaining patients continued to have inducible ventricular tachycardia. Ventricular tachycardia cycle length and right ventricular effective refractory period both progressively increased significantly over baseline, starting on day 1. The 15 patients who remained in the study had no significant side effects during the loading period.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma.

To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-alpha and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-alpha was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-alpha (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-alpha and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p less than 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p less than 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p less than 0.001) and a pretreatment CD4 cell count greater than or equal to 200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-alpha and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.

Acquired Immunodeficiency Syndrome

Benefit and risks of long-term amiodarone therapy for sustained ventricular tachycardia/fibrillation: minimum of three-year follow-up in 145 patients.

Our experience with amiodarone therapy in 145 consecutively referred patients with medically refractory sustained ventricular tachycardia and/or fibrillation treated for at least 3 years was reviewed. Ninety-seven had sustained ventricular tachycardia; the remaining 48 patients were survivors of sudden cardiac death. The patients had a mean of 3.7 +/- 1.4 unsuccessful anti-arrhythmic drug trials before initiation of amiodarone. The initial doses of amiodarone averaged 845 +/- 258 mg for the first 2 weeks and 56% of all patients received a type I antiarrhythmic drug in addition to amiodarone during the initial phase of therapy. The average maintenance dose of amiodarone was 410 +/- 187 mg per day. All patients were followed for a minimum of 3 years or until death or withdrawal from therapy. The maximum follow-up was a period of 8 years. Thus, the average duration of amiodarone therapy was 39 +/- 26 months, representing 472 patient years of therapeutic time on amiodarone. The incidence of deaths either caused by a documented ventricular tachyarrhythmia or presumed to result from an arrhythmic cause was 5.5% in the first year and 3.4% in each of the second and third years of follow-up. During the entire period of follow-up, 56 patients died of all causes (38.6% of the study population). Survival over the follow-up period was influenced significantly by left ventricular function, as judged by either New York Heart Association Functional Class or objective assessment of left ventricular ejection fraction, which was available in 102 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Assessment of coronary venous bypass graft function using krypton-81m.

Fifteen patients with intractable angina pectoris underwent coronary angiography and coronary arterial bypass graft surgery. After the operation, a continuous infusion of krypton-81m was delivered into each graft. A gamma camera and multichannel analyzer were used to record the regional myocardial distribution of perfusion provided by each graft. The disappearance of myocardial activity at the end of each infusion was used to calculate the flow per unit volume in the myocardial distribution provided by each vessel. Myocardial perfusion provided by the grafts to all the major coronary arteries were recorded individually as high spatial resolution images. Myocardial flow rates in the distribution of each graft were measured using the washout of krypton-81m. The rates were 0.5 to 2.0 ml/g per min in the 13 patients with no evidence of previous myocardial infarction. Krypton-81m was infused into grafts to the left anterior descending coronary artery in two patients with a history and electrocardiographic evidence of previous anterior myocardial infarction. The grafts provided poor perfusion to the anterior and apical portions of the ventricles. An experimental model of myocardial perfusion was used to demonstrate that the washout of krypton-81m can be used to measure flow per unit volume within or above the physiologic range.

Angina Pectoris

Survival rates after enucleation of eyes with malignant melanoma.

We investigated the rates of mortality for several types of malignant melanomas for evidence that surgery accelerates metastasis. Additionally, we reanalyzed uveal melanoma survival rates from the Armed Forces Institute of Pathology. Our computations showed higher death rates in years two to five after diagnosis than in years one or six to ten. The same pattern of a peak mortality in the early years after diagnosis and lower rates six to ten years thereafter was seen in all tumor types studied. Our analysis of survival rates produced no evidence to alter the existing pattern of treatment for malignant melanoma of the uvea.

Eye Neoplasms

Emphysematous gastritis in a leukemic child.

Emphysematous gastritis associated with gram-negative sepsis is described in a leukemic child on chemotherapy and steroids. Bubbly-appearing air and thickening of the gastric wall were radiographically demonstrated. This is analogous to the demonstration of air within the thickened bowel wall in necrotizing enterocolitis, which is not unusual in seriously ill leukemic children. Gastric involvement has not been previously reported.

Child

Theophylline radioimmunoassay: synthesis of antigen and characterization of antiserum.

Antisera to theophylline (T) have been obtained by immunizing rabbits with a conjugate of 8-(3-carboxypropyl)-1,3-dimethylxanthine and bovine serum albumin. Comparison of 50% displacement values indicated good selectivity for T vs. a number of other xanthine derivatives. An analytical procedure using this antiserum can measure 200 pg of T and direct analysis of 0.1 mug/ml in plasma or 0.02 mug/ml in saliva is feasible.

Animals

Studies on the intracisternal A-type particles in mouse plasma cell tumors: induction of maturation of the particles.

Maturation of the intracisternal A-type particle found in two mouse plasma cell tumors was induced by treating the cells in culture with IDU-DMSO or with DMSO only. Morphologically, the mature particles with electron-dense nucleoids closely resembled the mature particles described in human tumor cell lines treated in a like manner. They also closely resembled the virus that has been described in guinea pig leukemias. It was not possible to demonstrate infectivity of the mature particle, as latent intracisternal A-type particles induced by IDU were found in the mouse cells presumed to be free of virus. The biochemical studies did not show distinct new peaks of virus-specific particles in sucrose density gradients when the particles in the treated cells were compared with the particles of the untreated cells. There was a difference in the density of the particles observed in the induced cells (1.2) and those of the control cells (1.185). This may reflect the difficulty of separating mature and immature particles. Analysis of the RNA present in the particles showed that the ratio of heavy-molecular-weight RNA in activated cells to the predominant species (21S) is much greater than that in control cells. Detectable levels of enzyme activity were not found in the induced particles. This could be due to too low a concentration of particles in the preparations.

Animals

Prophylaxis of varicella in children with neoplastic disease: comparative results with zoster immune plasma and gamma globulin.

The incidence and severity of varicella following a close family contact were evaluated in children with neoplastic diseases who received prophylaxis either with commerical gamma globulin or with zoster immune plasma, as compared to patients who did not receive any prophylaxis. In the untreated group, all 14 patients developed varicella, complicated by 1 case of encephalitis and 2 cases of fatal pneumonia. In the group of 17 patients who received 0.6-1.2 ml/kg body weight of gamma globulin, 16 developed varicella, complicated by pneumonia in 2 cases, with 1 death. In the third group of 27 patients who received 10 ml/kg body weight of zoster immune plasma (ZIP), obtained from healthy adults convalescing from herpes zoster, there were only 8 cases of varicella, all very mild. Thus, prophylaxis with ZIP significantly reduced the incidence of clinical varicella (p less than 0.01) and attenuated the severity of its course.

Antineoplastic Agents